Authors: Kunig, Verena B. K.
Potowski, Marco
Klika Škopić, Mateja
Brunschweiger, Andreas
Title: Scanning protein surfaces with DNA-encoded libraries
Language (ISO): en
Abstract: Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points.
Subject Headings: DNA-encoded libraries
Drug development
Protein-protein interactions
Issue Date: 2020-12-09
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Appears in Collections:Medizinische Chemie und Chemische Biologie

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